Abstract: Objective To investigate the inhibitory effects of triterpenes compound of cortex periplocae (TCCP) on N-nitrosomethylbenzylamine (NMBA) -induced esophageal tumorigenesis in F344 rats and its mechanism. Methods Ninety male F344 rats (5~6 weeks of age) were randomly divided into four groups:rats were treated with 0.5 mg/kg NMBA only as model group and rats received NMBA 0.5 mg/kg s.c.plus TCCP 20 mg/kg i.m.as TCCP treatment groups and those treated with soya oil 1 ml/kg intramuscularily(i.m.) acted as soya oil control and normal control groups.The administration of drugs was scheduled as below:three times a week for 5 weeks.At 9th,15th and 25th week,5 rats from normal group and soya oil control group and 10 rats from model group and TCCP treatment group were euthanized by pentobarbital sodium and subjected to gross necropsy,respectively.The esophagus of each rat was excised and opened longitudinally.Then esophagus were fixed in 10% phosphate-buffer formalin solution,and routinely embedded in paraffin for HE staining to observe the pathological changes of esophageal tissues,while the expression of c-myc mRNA was detected by RT-PCR.Western blot was used to investigate the protein expression of GSK-3β and β-catenin in the esophageal epithelium. Results There were no abnormal change in normal and soya oil groups among bioassay.It was observed that the expression of β-catenin was slightly present in normal mucosa of esophagi of the rats which were untreated with NMBA,and then was significantly increased by administering NMBA from week 9 to 25 (P<0.05).The up-regulated β-catenin expression was decreased significantly by TCCP treatment at each check-point (P<0.05).The expression of GSK-3β was rich in normal mucosa of esophagus,but was decreased significantly by administering NMBA,and was lowest at 25th week (P<0.05).The decreased protein level of GSK3β was significantly elevated by TCCP treatment at each check-point (P<0.05).The gene expression of c-myc of esophageal epithelium in NMBA control group was significantly increased at 9th,15th,25th week compared with normal control (P<0.05).TCCP suppressed the mRNA expression of c-myc at both 9th and 15th week (P<0.05),but not at 25th week. Conclusion TCCP inhibited NMBA-induced rat esophageal carcinogenesis probably via activating GSK-3β expression and suppressing β-catenin and c-myc expression.